Optics: measuring and testing – By dispersed light spectroscopy – With sample excitation
Reexamination Certificate
2001-03-27
2004-02-10
Chang, Andrey (Department: 2872)
Optics: measuring and testing
By dispersed light spectroscopy
With sample excitation
C436S172000, C435S288700, C382S168000, C422S052000
Reexamination Certificate
active
06690461
ABSTRACT:
TECHNICAL FIELD
The present invention relates to processing of microarray experiment data, particularly, to a method for visually displaying useful microarray information.
BACKGROUND ART
Conventionally, as a method for obtaining useful information from data resulting from experiments using microarrays (also referred to as biochips), the following methods are known. Specifically, a method in which sample spots extracted and sorted under specific conditions are displayed as an image of pixels representing values standardized for each microarray, and a method in which sample spots are classified based on a statistical analysis (a clustering analysis) of luminescent intensity data of the sample spots between multiple microarrays.
Although conventional methods are effective in providing intuitive information via an image of a collection of numerous samples immobilized on microarrays or in providing statistical information by a clustering analysis, they are not always effective in finding out information that is important in terms of molecular biology, which is present in a scarce amount buried in the huge amount of microarray experiment information. It has not been long since microarrays have begun to be used in molecular biological experiments, and in order to elucidate facts unanticipated by users from the microarray information, there is a need of obtaining means for displaying information from various points of view.
The objective of the present invention is to realize a user interface which is capable of effectively processing a huge amount of microarray information and displaying it as a graph, to achieve a system capable of discovering scarce but important information in terms of molecular biology buried in the huge amount of microarray information.
DISCLOSURE OF THE INVENTION
The present invention is provided with: a “microarray primary database” for accumulating information of spots immobilized on microarrays and luminescent intensity data of the numerous sample spots obtained by a microarray analysis; a “micorarray data extracting/processing program” for extracting, under specific conditions, a data set including a plurality of samples and processing it for displaying a graph; a “micorarray information display program” for displaying a three-dimensional graph where the sample spots and the microarrays sorted under various conditions are assigned to X- and Y-axes and luminescent intensities to Z-axis; a method for not missing any signals in the huge amount of information in displaying the three-dimensional graph produced by the microarray information display program; and a cache processing software for a fast display of the information.
The luminescent intensity information of the sample spots obtained with the microarrays is standardized for each microarray. Then, the differences of the standardized luminescent intensities of the sample spots from a standardized luminescent intensity of a sample spot of interest are displayed as a graph. Accordingly, information can be compared without being biased by a difference between the microarrays (biochips) caused by experimental errors or a difference between samples caused by physical properties. Selection of parameters for displaying without missing any important information in the data or for displaying information from various points of view can be realized with a user interface.
A method of the present invention for displaying microarray information by which information of accumulated luminescent intensities of numerous sample spots obtained by a microarray analysis is displayed, comprises the steps of: selecting a set of samples as subjects of a test; acquiring accumulated luminescent intensities of the sample spots on each of microarrays, the sample spot corresponding to the set of samples; sorting the set of samples and the set of microarrays to which the sample spots belong, under predetermined conditions; and displaying a three-dimensional graph by assigning the set of sorted samples and the set of sorted microarrays to X-axis and Y-axis, and the accumulated luminescent intensities to Z-axis.
Preferably, the accumulated luminescent intensities are based on standardized luminescent intensities which have undergone a first standardization using a control spot located on each microarray for a purpose of eliminating experimental errors within the microarray to which the sample spot belongs, and a second standardization using a standard marker spot located on each microarray for the purpose of eliminating experiment errors between the microarrays and for the purpose of equalizing an intentionally adjusted range of luminescent intensities.
Preferably, the standardized accumulated luminescent intensities have undergone, in addition to the first and second standardizations, a third standardization in view of the luminescent intensity ranges between the samples based on the accumulated luminescent intensities of the sample spots belonging to the same sample.
In displaying microarray information, it is advantageous that the set of samples are sorted according to their accumulated luminescent intensities on a specific microarray. In addition, it is advantageous that after the set of samples are sorted according to their accumulated luminescent intensities on a specific microarray, the set of microarrays are sorted according to a total difference of the accumulated luminescent intensities of their samples from that of the specific micorarray. Alternatively, it is advantageous that the set of microarrays are sorted according to an accumulated luminescent intensity of a specific sample. In addition, it is also advantageous that after the set of microarrays are sorted according to an accumulated luminescent intensity of a specific sample, the set of samples are sorted according to a total difference of the accumulated luminescent intensities on the microarrays from that of the specific sample. In either case, the accumulated luminescent intensities are preferably standardized by the first, second or third method. The total difference may be a standard deviation or a mean deviation of the accumulated luminescent intensities.
Furthermore, it is also advantageous that a two-dimensional graph is displayed by slicing out a cross-sectional plane from the three-dimensional graph displayed by the method for displaying microarray information.
According to the present invention, meaningful information can visually be obtained from luminescent intensity information obtained with microarrays. Even an extremely small signal included in the mass amount of information can be displayed without being missed.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS.
1
(
a
) to
1
(
c
) are illustrations showing exemplary microarrays, where FIG.
1
(
a
) is a schematic view showing a step of producing the microarray; FIG.
1
(
b
) is a schematic plan view of the produced microarrays; and FIG.
1
(
c
) is a schematic view showing the microarray after a reaction such as a hybridization reaction.
FIG. 2
is a block diagram showing a system for displaying microarray information according to one embodiment of the present invention.
FIG. 3
is a diagram showing exemplary data structures of a microarray primary database.
FIG. 4
is a flowchart of a process for producing data for displaying a graph.
FIG. 5
shows diagrams illustrating a general idea of an example of producing a three-dimensional graph.
FIG. 6
shows exemplary two-dimensional graphs obtained by slicing the three-dimensional graph.
FIG. 7
is a view showing an exemplary interface for a user to perform settings to display a graph.
FIGS.
8
(
a
) and
8
(
b
) are diagrams showing an exemplary comparison of expression profiles by using a three-dimensional graph display of the invention.
REFERENCES:
patent: 5744320 (1998-04-01), Sherf et al.
patent: 5798263 (1998-08-01), Wood et al.
patent: 5907820 (1999-05-01), Pan
patent: 2-168161 (1990-06-01), None
patent: 2-271827 (1990-11-01), None
patent: 110-75087 (1999-03-01), None
patent: 11-342000 (1999-08-01), None
Mizuno Katsuya
Tamura Takuro
Yoshii Jyunji
A. Marquez, Esq. Juan Carlos
Chang Andrey
Fisher Esq. Stanley P.
Hitachi Software Engineering Co. Ltd.
Reed Smith LLP
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